Pharmacokinetics of tacrolimus co-administered with adefovir dipivoxil to liver transplant recipients.

Abstract

BACKGROUND:

Adefovir dipivoxil has activity against wild-type and lamivudine-resistant hepatitis B virus (HBV) and is frequently used to manage HBV infection in transplant recipients. Calcineurin inhibitors are a central component of immunosuppressive therapy.

AIMS:

Study GS-02-531 was an open-label, multicentre drug interaction trial to examine potential drug interactions between adefovir and tacrolimus in stable post-transplant recipients.

MATERIALS AND METHODS:

Sixteen non-HBV-infected post-transplant recipients with median age 45.5 years (69% male, 44% Caucasian, 50% Hispanic and 6% Black) and stable hepatic and renal function on a stable daily dose of tacrolimus (2-10 mg total daily dose) were studied before (tacrolimus alone) and after co-administration of adefovir 10 mg daily for 14 days (Days 1-14). Pharmacokinetic (PK) analyses utilized non-compartmental methods.

RESULTS:

The median elimination half-life of tacrolimus was 14.47 and 12.59 h for Day 0 and Day 14 respectively. The geometric mean ratios for tacrolimus on Day 14 vs Day 0 were 105.2% [90% confidence interval (90% CI): 89.8-123%] for C(max) and 106.4% (90% CI: 92.9-122%) for AUC(tau). Both 90% CIs for the ratios were contained within the predefined lack of interaction bounds of 80 and 125% (i.e. within the bounds for the equivalence assessment), indicating that these PK parameters of tacrolimus are not significantly altered by co-administration of adefovir. Similarly, the observed adefovir PK parameters after 14 days of co-administration with tacrolimus were comparable to historical data in non-transplant patients receiving adefovir alone. Serum creatinine values were stable during the study period.

CONCLUSION:

There is no significant PK interaction between tacrolimus and adefovir co-administered to liver transplant recipients for 14 days.

• Authors: Norah A Terrault, Tram T Tran, Eugene Schiff, Brendan M McGuire, Robert S Brown Jr, Rebecca Tupper, Srini Ramanathan, Jeffrey Enejosa, Lijie Zhong, Jian Zong, Study 531 Team
• Journal: Liver international : official journal of the International Association for the Study of the Liver (Liver Int) Vol. 29 Issue 8 Pg. 1178-83 (Sep 2009) ISSN: 1478-3231 [Electronic] United States
• PMID: 19486291 (Publication Type: Clinical Trial, Journal Article, Multicenter Study)

Chemical References

• Antiviral Agents
• Immunosuppressive Agents
• Organophosphonates
• Adenine
• adefovir dipivoxil
• Tacrolimus

Topics

• Adenine (analogs & derivatives, therapeutic use)
• Adolescent
• Adult
• Aged
• Antiviral Agents (therapeutic use)
• Drug Interactions
• Drug Therapy, Combination
• Female
• Half-Life
• Hepatitis B (prevention & control)
• Humans
• Immunosuppressive Agents (pharmacokinetics)
• Liver Transplantation
• Male
• Middle Aged
• Organophosphonates (therapeutic use)
• Tacrolimus (pharmacokinetics)
• Young Adult